Platelet aggregation requires the presence of extracellular fibrinogen and divalent cations. Recently it was shown that platelet stimulation exposes receptors for fibrinogen on the platelet's surface. It has also been suggested that the binding of fibrinogen to these receptors is required for aggregation to occur. The goals of this study are to identify, isolate, and characterize the platelet fibrinogen receptors and to examine the role of divalent cations in fibrinogen binding. Studies are in progress examining the role of prostaglandins in the exposure of fibrinogen receptors. Treatment of platelets with aspirin or indomethacin decreases the number of fibrinogen receptors exposed by ADP and epinephrine by 40 to 60%. This deficit can be corrected by the simultaneous incubation of aspirin treated platelets with the agonist and the prostaglandin endoperoxide PGH2. Experiments are also in progress to determine the structural features of fibrinogen required for platelet binding, to identify and isolate the fibrinogen receptor, and to determine the role of divalent cations in fibrinogen binding. The results of these studies should provide important new information regarding the physiology of platelet aggregation. Because platelet aggregation has been implicated in the pathogenesis of atherosclerotic vascular disease, understanding the mechanisms involved in platelet aggregation may prove useful in the design of new specific therapeutic approaches to this disease process.